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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 43  |  Issue : 2  |  Page : 46-51

Low serum free and total tri-iodothyronine hormones as possible prognostic factors in liver cirrhotic patients because of chronic hepatitis C


Hepatogastroenterology and Endoscopy Unit, Department of Internal Medicine, Tanta University Hospital, Tanta, Egypt

Date of Submission14-Nov-2014
Date of Acceptance27-Jan-2015
Date of Web Publication3-Jun-2015

Correspondence Address:
Mohamed A Tawfik
Hepatogastroenterology and Endoscopy Unit, Department of Internal Medicine, Tanta University Hospital, Tanta
Egypt
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DOI: 10.4103/1110-1415.158048

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  Abstract 

Background and aim
Liver and thyroid hormones are powerfully correlated; thus, thyroid hormone abnormalities are found in patients with liver diseases. We evaluated serum thyroid hormone levels in chronic hepatitis C (CHC) cirrhotic patients with and without hepatic encephalopathy.
Patients and methods
Our study was carried out on 100 patients with CHC-related liver cirrhosis (66 men and 34 women). They were divided into three groups: group I, which included 40 patients proved to have liver cirrhosis because of CHC with hepatic encephalopathy (26 men and 14 women), group II, which included 60 patients proved to have liver cirrhosis because of CHC without hepatic encephalopathy (40 men and women), and group III, the control group, which included 20 healthy individuals (12 men and eight women). Free tri-iodothyronine (FT3), free thyroxine (FT4), total T3, total T4, and thyrotropine-stimulating hormone (TSH) were tested.
Results
Group I and group II showed a significant decrease in T3 and FT3 levels compared with the controls (group III), whereas there was no difference in serum T4, TSH, and FT4 levels. All the patients (group I) had significantly reduced levels of T3 and FT3 compared with group II, whereas there was no difference in T4, FT4, and TSH levels.
Conclusion
Patients with CHC cirrhosis have significantly lower serum FT3 and T3. Patients with hepatic encephalopathy were found to have very low serum T3 and FT3 levels. Decreased serum T3 and FT3 levels, together with a prolonged prothrombin time and hypoalbuminemia, therefore appear to be characteristic of decompensated cirrhotic patients prone to developing hepatic encephalopathy.

Keywords: cirrhosis, hepatic encephalopathy, thyroid function tests


How to cite this article:
El-Sawy AAA, Tawfik MA. Low serum free and total tri-iodothyronine hormones as possible prognostic factors in liver cirrhotic patients because of chronic hepatitis C. Tanta Med J 2015;43:46-51

How to cite this URL:
El-Sawy AAA, Tawfik MA. Low serum free and total tri-iodothyronine hormones as possible prognostic factors in liver cirrhotic patients because of chronic hepatitis C. Tanta Med J [serial online] 2015 [cited 2018 Jan 23];43:46-51. Available from: http://www.tdj.eg.net/text.asp?2015/43/2/46/158048


  Introduction Top


Liver cirrhosis is a slowly progressing disease in which healthy liver tissue is replaced with scar tissue. It is the end result of the fibrogenesis that occurs with chronic liver injury. The destruction of hepatic normal architecture and loss of liver cells prevent the liver from functioning normally [1] .

Liver cirrhosis may result from multifactorial liver diseases, mainly chronic hepatitis C virus (HCV), chronic hepatitis B virus, alcohol or drug induced, hemochromatosis, Wilson disease, nonalcohol fatty liver disease, and a-1-antitrypsin deficiency [1] .

In western countries, the prevalences of alcoholic cirrhosis, nonalcohol fatty liver disease, and autoimmune liver diseases are increasing, whereas in developing countries, hepatitis viruses B and C are the predominant risk factors for liver cirrhosis [2] . In Egypt, the prevalence of HCV infection among the general population has been estimated to be around 14% [3],[4] .

Liver cirrhosis may be compensated or decompensated. Decompensated cirrhosis may be manifested by jaundice, ascites, hepatic encephalopathy, bleeding varices, hepatorenal syndrome, hyponatremia, and spontaneous bacterial peritonitis [5] .

Liver and thyroid hormones are powerfully correlated; thus, thyroid hormone abnormalities are found in patients with liver diseases, although they are clinically euthyroid [6] . The liver plays an important role in the metabolism of thyroid hormones, being involved in their conjugation, excretion, and peripheral deiodination, and in synthesizing thyroid-binding globulin [7],[8] . The association between chronic liver diseases and thyroid dysfunctions has often been reported, but there is limited information available on the association between thyroid dysfunctions and decompensated liver cirrhosis with hepatic encephalopathy. The available reported studies have shown that T4 levels are usually within normal limits, but, as cirrhosis progresses, FT4 levels increase secondary to decreased serum levels of thyroxine-binding protein [9] and at the same time, other studies reported that T3 and FT3 concentrations are usually decreased in correlation with the severity of liver cirrhosis, but this is still controverted [10] .

To our knowledge, there have been limited studies comparing thyroid dysfunctions in patients with decompensated cirrhosis and those with cirrhosis with the complication of hepatic encephalopathy.

In this study, we will investigate thyroid hormone levels in chronic hepatitis C (CHC)-related cirrhotic patients with and without hepatic encephalopathy. At the same time, we will attempt to determine whether or not thyroid function tests may be a useful prognostic indicator for the development of hepatic encephalopathy in patients with decompensated cirrhosis.


  Patients and methods Top


Our study was carried out on 100 patients with CHC-related liver cirrhosis (66 men and 34 women, mean age 54.5 ± 17.5 years, range 37-72 years); they were consecutively admitted to the Hepatology Unit of the Internal Medicine Department at Tanta University Hospitals. Research ethics committee at Faculty of medicine of Tanta University Hospital approved this research (code:2687/08/14).

An informed consent was obtained from all participants. All the records were confidential. The results of this research will be used only for scientific purposes. No unexpected risks occured during the course of the research.

The patients studied and the control participants were divided into three groups:

Group I included 40 patients proved to have liver cirrhosis because of CHC with hepatic encephalopathy (26 men and 14 women, mean age 59.5 ± 12.5 years, range 47-72 years); this group was divided into two subgroups: subgroup Ia, which included 20 cirrhotic patients with hepatic encephalopathy and still surviving (survivors) (mean age 59.5 ± 12.5 years, range 47-72 years), and subgroup Ib, which included 20 cirrhotic patients with hepatic encephalopathy, but who had died during the course of treatment (nonsurvivors) (mean age 60 ± 7 years, range 53-67 years).

Group II included 60 patients proved to have liver cirrhosis because of CHC without hepatic encephalopathy (40 men and 20 women, mean age 47.5 ± 10.5 years, range 37-58 years); this group was divided into three subgroups according to Child's Pugh classification: subgroup IIa, which included 20 patients with Child's Pugh class A (mean age 56.5 ± 9.5 years, range 37-56 years), subgroup IIb, which included 20 patients with Child's Pugh class B (mean age 50.5 ± 7.5 years, range 43-58 years), and subgroup IIc, which included 20 patients with Child's Pugh class C (mean age 49.5 ± 8.5 years, range 41-58 years).

Group III, the control group, included 20 healthy individuals (12 men and eight women, mean age 51.5 ± 15.5 years, range 36-67 years).

All the patients studied were proved to have CHC-related liver cirrhosis. The exclusion criteria of our study were as follows: liver cirrhosis with negative HCV PCR, abnormal findings on clinical thyroid examination, a present or a previous history of thyroid disease, taking any drug known to affect thyroid function including recent or previous history of interferon therapy, abnormal findings in thyroid ultrasound, and finally antithyroid AB-positive patients.

The diagnosis of cirrhosis-related hepatitis C was made on the basis of a full assessment of case history, a full clinical examination, liver biochemical profile, ultrasound findings, liver fibroscan or liver biopsy (if possible), and anti-HCV antibodies.

The functional severity of the liver injury was determined on the basis of the Child-Pugh grading system.

Thyroid hormones dysfunctions: In all cases, blood samples for hormone determinations were drawn in the morning after an overnight fast for the measurement of free tri-iodothyronine (FT3), free thyroxine (FT4), total T3, total T4, and thyrotropine-stimulating hormone (TSH).

Statistical analysis

All patients' data were tabulated and processed using SPSS 10.0 (Statistical Package for Science and Society, Chicago, USA). Student's t-test was used to compare the continuous variables between two groups. The analysis of variance was used to test the significance of continuous variables within groups. All values are reported as mean ± SD. In all tests, the P value was considered significant if less than 0.05.


  Results Top


As shown in [Table 1], our patients with hepatic encephalopathy (group I) and all cirrhotic patients (group II) showed a significant decrease in T3 and FT3 levels compared with the controls (group III) (63.55 ± 15.66 vs. 95.55 ± 25.72 and 70.44 ± 21.76 vs. 95.55 ± 25.72 ng/dl with P < 0.0001 for T3 and 1.023 ± 0.2005 vs. 3.061 ± 0.5245 and 2.151 ± 0.6698 vs. 3.061 ± 0.5245 pg/ml with P < 0.0001 for FT3, respectively), whereas there was no difference in serum T4, TSH, and FT4 levels.
Table 1 Comparison between all cirrhotic patients and all hepatic encephalopathy patients with control participants in thyroid functions

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At the same time, as shown in [Table 2], we found that all cirrhotic patients with hepatic encephalopathy (group I) had significantly reduced levels of T3 and FT3 compared with all cirrhotic patients without hepatic encephalopathy (group II) (P = 0.0392 for T3 and <0.0001 for FT3), whereas there was no difference in T4, FT4, and TSH levels.
Table 2 Comparison between all cirrhotic patients and hepatic encephalopathy patients in thyroid functions

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Patients with decompensated Child C cirrhotic had significantly lower serum T3 and FT3 levels than the Child A and Child B groups (P < 0.0001). No significant differences were observed when serum T4, FT4, and TSH levels were compared among Child A, Child B, and Child C groups as shown in [Table 3].
Table 3 Comparison between all cirrhotic patients in thyroid functions and Child's classifi cation

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Our results as presented in [Table 4], which shows that no significant differences in T3, T4, TSH, FT3, and FT4 levels were observed between survivors (group Ia) and nonsurvivors (group Ib) with hepatic encephalopathy.
Table 4 Comparison between surviving and nonsurviving hepatic encephalopathy patients in thyroid functions

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At the same time, both survivors (group Ia) and nonsurvivors (group Ib) with hepatic encephalopathy had significantly decreased T3 and FT3, whereas there was no significant difference in T4, FT4, and TSH levels as shown in [Table 5].
Table 5 Comparison between surviving and nonsurviving hepatic encephalopathy patients with Child's C patients in thyroid functions

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  Discussion Top


The liver plays an important role in the metabolism of thyroid hormones, being involved in their conjugation, excretion, and peripheral deiodination, and in synthesizing thyroid-binding globulin [7],[8] .

The association between chronic liver diseases and thyroid dysfunctions has often been reported, but limited information is available on the association between thyroid dysfunctions and decompensated liver cirrhosis with hepatic encephalopathy. The available reported studies have shown that T4 levels are usually within normal limits, but, as cirrhosis progresses, FT4 levels increase secondary to decreased serum levels of thyroxine-binding protein [9] and at the same time, other studies have reported that T3 and FT3 concentrations are usually decreased in correlation with the severity of liver cirrhosis, but this is still controverted [10] .

Thyroid dysfunction has been reported previously in a variety of nonthyroid illnesses including liver, pulmonary, and renal neoplastic disease, severe systemic illness, fasting, malnutrition, postoperative state, physical trauma, and acute infections. Low total and free T3 with normal total T4 and thyrotropin concentrations in the absence of clinical hypothyroidism have frequently been reported in patients with nonthyroidal illnesses [11],[12],[13] . Several researches have been performed to assess the relationship between liver disease and thyroid hormones [7],[8],[11],[14] .

The results of our study showed that the patients with hepatic encephalopathy studied (group I) and all cirrhotic patients (group II) showed a significant decrease in T3 and FT3 levels compared with the controls (group III), with P value less than 0.0001 for T3 and FT3, whereas there was no difference in serum T4, TSH, and FT4 levels.

These results are in agreement with those of Hepner and Walfish, who reported a significant inverse correlation between serum T3 concentrations and the severity of liver dysfunction. A progressive decrease in T3 levels in chronic liver diseases has been considered to be indicative of a poor prognosis [14],[15],[16] .

The authors ascribed this finding to reduced conversion of T4 into T3 and impaired metabolism of thyroxine-binding proteins [14],[15],[16] .

In the present study, we found a significant decrease in both FT3 and T3 levels in accordance with the severity of liver dysfunction according to Child's classification, where patients with Child's C showed significantly decreased FT3 and T3 levels than Child's A and Child's B patients. These results are similar to those reported by many researchers [17],[18],[19] , who reported a decrease in FT3 and T3 according to the severity of the disease, and a good correlation between T3 concentrations, serum albumin, and prothrombin time. These results suggest that serum T3 and FT3 concentrations may be considered a sensitive index of hepatic function in liver disease. These results are also in agreement with those of Kayacetin et al. [19] , who compared cirrhotic patients with normal individuals and chronic hepatitis patients. They suggested that T3 serum levels are inversely parallel to the severity of liver dysfunction [8] .

Our study compared cirrhotic patients with and without hepatic encephalopathy and obtained findings similar to those of Kayacetin et al. [19] , who determined alterations in thyroid hormone levels in nonalcoholic decompensated cirrhotic patients with and without hepatic encephalopathy and found a significant reduction in serum FT3 in nonalcoholic cirrhotic patients compared with a control group, the lowest values being found in patients with hepatic encephalopathy. Low FT3 levels may be because of reduced extrathyroidal T4-to-T3 conversion, the mechanism being inversely related to the degree of hepatic dysfunction.

At the same time, our results are similar to those found by Kayacetin et al., [19] as we found no significant difference in functional thyroid parameters between patients surviving and not surviving hepatic encephalopathy. These findings are in contrast to those of Guven et al. [17] , who reported lower T3 levels in patients who died than in patients who survived. The reason for this difference is not clear.


  Conclusion Top


Patients with CHC cirrhosis have significantly lower serum FT3 and T3 than noncirrhotics. At the same time, patients with decompensated liver disease complicated by hepatic encephalopathy subsequent to CHC cirrhosis were found to have very low serum T3 and FT3 levels. Reduced serum T3 and FT3 levels, together with a prolonged prothrombin time and hypoalbuminemia, therefore appear to be characteristic of decompensated cirrhotic patients prone to developing hepatic encephalopathy.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

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El-Zayadi A, Abaza H, Shawky S, et al. Prevalence and epidemiological features of hepatocellular carcinoma in Egypt; a single center experience. Hepatol Res 2001; 19:170-179.  Back to cited text no. 3
    
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Esmat G. Hepatocellular carcinoma: the magnitude of the problem in Egypt, 6th International Conference of Oncology, Surgery and Gastroenterology. Towards a healthy liver in Egypt. 10-12 April:54; 2002.  Back to cited text no. 4
    
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Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia and mortality among patients on liver transplant waiting list. N Engl J Med 2008; 359:1018-1026.  Back to cited text no. 5
    
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Malik R, Hodgson H. The relationship between the thyroid gland and the liver. QJM 2002; 95:559-569.  Back to cited text no. 6
    
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Babb RR. Associations between diseases of the thyroid and the liver. Am J Gastroenterol 1984; 79:421- 423.  Back to cited text no. 7
    
8.
Borzio M, Caldara R, Ferrari C, et al. Thyroid function tests in chronic liver disease: evidence for multiple abnormalities despite clinical euthyroidism. Gut 1983; 24:631- 636.  Back to cited text no. 8
    
9.
Bianchi GP, Zoli M, Marchesini G, et al. Thyroid gland size and function in patients with cirrhosis of the liver. Liver 1991; 11:71-77.  Back to cited text no. 9
    
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Sheridan P. Thyroid hormones and the liver. J Clin Gastroenterol 1983; 12:797-818.  Back to cited text no. 10
    
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Chopra IJ, Soloman DH, Hepner GW, Morgenstein AA. Mis-leadingly low free thyroxine index and usefulness of reverse tri-iodothyronine measurement in non thyroidal illnesses. Ann Intern Med 1979; 90: 905-912.  Back to cited text no. 11
    
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Kaptein EM, Weiner JM, Robinson WJ, Wheeler WS, Nicoloff JT. Relationship of altered thyroid hormone indices to survival in nonthyroidal illnesses. Clin Endocrinol 1982; 16:565- 574.  Back to cited text no. 12
    
13.
Bermudez F, Surks MI, Oppenheimer JH. High incidence of de-creased serum triidothyronine concentration in patients with nonthyroidal disease. J Clin Endocrinol Metab 1975; 41:27-40.  Back to cited text no. 13
    
14.
Hepner GW, Chopra IJ. Serum thyroid hormone levels in pa-tients with liver disease. Arch Intern Med 1979; 139:1117-1120.  Back to cited text no. 14
    
15.
Walfish PG, Orrego H, Israel Y, Blake J, Kalant H. Serum tri-iodothyronine and other clinical and laboratory indices of alcoholic liver disease. Ann Intern Med 1979; 91:13-16.  Back to cited text no. 15
    
16.
Klachko DM, Johnson ER. The liver and circulating thyroid hormones. J Clin Gastroenterol 1983; 5:465-471  Back to cited text no. 16
    
17.
Guven K, Kelestimur F, Yucesoy M. Thyroid function tests in non-alcoholic cirrhotic patients with hepatic encephalopathy. Eur J Med 1993; 2:83-85.  Back to cited text no. 17
    
18.
Thobe N, Pilger P, Jones MP. Primary hypothyroidism masquerading as hepatic encephalopathy: case report and review of the literature. Postgrad Med J 2000; 76:424-426.  Back to cited text no. 18
    
19.
Kayacetin E, Kisakol G, Kaya A. Low serum total thyroxine and free T3 in patients with hepatic encephalopathy due to non-alcoholic cirrhosis. Swiss Med Wkly 2003; 133:210-213.  Back to cited text no. 19
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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